3rd Edition of Dementia World Conference 2026

Abstract

Depression has become a major global public health challenge, with existing drugs suffering from limitations such as delayed onset and significant side effects. Based on the patented technology and pharmacological research of Professor Cai Decheng's team, this study systematically explores the antidepressant effects and pleiotropic values of total flavonoid extract from Tagetes patula L. Results show that: T. patula extract significantly improves depressive-like behaviors by inhibiting central nervous system (CNS) sterile inflammation and repairing damaged brain neurons, with a daily intake of 10g achieving preventive and adjuvant therapeutic effects; its preparation process is simple and cost-effective (the total treatment cost per patient is only several thousand RMB), and it has been verified as highly safe through toxicological tests, enabling wide application in food, beverages and other daily products. Additionally, the extract possesses pleiotropic effects including pain relief, anti-carcinogenesis, emotional regulation, and extension of effective lifespan, providing a novel natural solution for human mental health and overall health protection.

Keywords: Tagetes patula extract; total flavonoids; antidepressant; neuroinflammation; pleiotropy; natural medicine1 Introduction1.1 Current Status and Challenges in Depression TreatmentAccording to the World Health Organization (WHO) prediction, depression will become the leading cause of disability worldwide by 2030, imposing a heavy burden on individuals and society. Currently used clinical antidepressants (e.g., selective serotonin reuptake inhibitors, SSRIs) have problems such as slow onset (needing 2-4 weeks), limited response rate (only about 60%), and obvious side effects (e.g., gastrointestinal reactions, sleep disorders), and fail to solve the recurrence problem in some patients. In recent years, the core role of neuroinflammation in the pathogenesis of depression has been widely confirmed: excessive secretion of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) induced by microglial activation impairs CNS synaptic function, leading to dysregulation of emotional regulatory pathways and forming a pathological cycle of "sterile inflammation-neuronal damage-depressive behaviors". This discovery provides a new direction for the development of natural drugs targeting anti-inflammation.1.2 Medicinal Value and Research Basis of Tagetes patulaTagetes patula L., an annual herb belonging to the Asteraceae family (genus Tagetes), is widely distributed across China and has been traditionally used for clearing heat and resolving phlegm, nourishing blood and unblocking meridians. Professor Cai Decheng's team has long been committed to the pharmacological research of T. patula extract, successfully preparing a high-activity extract with total flavonoid content ≥40% through optimized extraction technology, and verifying its potential values in antidepressant, anti-inflammatory, anti-cancer and other fields. Compared with traditional drugs and synthetic compounds, T. patula extract has the advantages of low toxicity, low cost, and easy use, and can achieve preventive health care functions through daily intake, which is consistent with the health concept of "preventing diseases before occurrence" and has broad application prospects.

2 Materials and Methods

2.1 Preparation Process of Tagetes patula ExtractReferring to the patented technology of Professor Cai Decheng's team (CN 107375376 A), the optimized preparation process is as follows:

1. Raw material processing: Select the whole plant of T. patula (roots, stems, leaves, flowers) and crush into 1-10 mesh coarse powder to ensure sufficient release of active ingredients;

1. Warm maceration extraction: Use purified water as solvent with a solid-liquid ratio of 1:8 (weight ratio), perform warm maceration extraction twice at 60-80℃ for 1 hour each time, and combine the extracts;

1. Purification and enrichment: Concentrate the extract to 1.5 times the weight of the raw material, add 95% ethanol to adjust the ethanol concentration to 70%, refrigerate at 4℃ for 12-24 hours, and centrifuge to collect the supernatant;

1. Extraction and drying: Extract the supernatant with water-saturated n-butanol 3-4 times, combine the extracts, and dry under reduced pressure (50℃) to obtain total flavonoid extract. The total flavonoid content is determined by colorimetry to be ≥40%.

This process does not require complex equipment, is suitable for industrial production, significantly reduces the cost of the extract, and lays a foundation for clinical promotion.

2.2 Safety and Toxicity Verification

A combination of in silico toxicology prediction and animal experiments was used to verify safety:

1. In vitro toxicity prediction: The acute toxicity of main flavonoid components (e.g., patuletin, quercetagetin) in T. patula was analyzed through the Protox-II web server. Results showed that most components were classified into toxicity class V (only possibly harmful) with no highly toxic components;

1. Animal safety experiment: SD rats were given intragastric administration of different doses of the extract (100-2000mg/kg) for 30 consecutive days. No obvious toxic symptoms were observed, and liver and kidney functions as well as blood routine indicators were normal, proving extremely low acute and subacute toxicity;

1. Population suitability screening: Special populations (e.g., people with spleen-stomach deficiency and cold, pregnant women, and those with allergic constitutions) should use it with caution, and the daily intake for healthy people should not exceed 10g as a safe range.

2.3 Efficacy Verification Methods

1. Antidepressant activity: Chronic unpredictable mild stress (CUMS) mouse model was used to evaluate the improvement of depressive-like behaviors through sucrose preference test, forced swimming test (FST), and open field test. Changes in the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the hippocampus were detected;

1. Anti-inflammatory mechanism: BV-2 microglial cells were cultured in vitro, and inflammation models were induced by LPS. The inhibitory effects of the extract on cell activation and inflammatory pathways (TLR4/NF-κB) were detected;

1. Pleiotropy verification: Pain relief effect was verified through pain model (acetic acid writhing test); anti-carcinogenic activity was evaluated by in vitro cancer cell proliferation assay (CCK-8 method); long-term intervention experiments were conducted to observe the impact on the quality of life and lifespan of mice.

3 Results and Analysis

3.1 Significant Antidepressant Efficacy

CUMS model experiments showed that the sucrose preference of mice in the T. patula extract intervention group (10g/kg per day) was significantly higher than that in the model group (P), the immobility time in forced swimming was shortened by 42.3% (P01), and the residence time in the central area of the open field test increased by 38.7% (P1), with effects superior to the positive drug fluoxetine. Molecular level detection confirmed that the extract could significantly reduce the concentrations of IL-1β, IL-6, and TNF-α in the hippocampus (decreased by 35.6%, 41.2%, and 38.9% respectively), inhibit microglial activation, and repair neuronal damage. Its mechanism is closely related to targeted blocking of sterile inflammation's invasion of brain nerves. Preliminary clinical observations showed that the effective rate of the extract in patients with mild to moderate depression was over 85% without obvious side effects, which was significantly better than traditional drugs.

3.2 Core Advantages: Safety, Convenience, and Low Cost

1. Safety: The extract is non-toxic and has no side effects, and can be added to beverages, pastries and other foods to achieve daily intake, meeting both therapeutic needs and preventing depression;

1. Convenience: The usage method is simple without professional operation, and a daily intake of 10g can achieve preventive effects, suitable for public popularization;

1. Economy: After industrial production, the total treatment cost per patient is only several thousand RMB, which is much lower than existing antidepressant drugs (annual cost over 10,000 RMB), significantly reducing the economic burden on patients.

3.3 Pleiotropic Values: From Single Treatment to Comprehensive Health Protection

1. Emotional regulation and personality improvement: By inhibiting the "upper fire-inflammation" pathway, the extract can reduce irritable emotions, promote calm personality, lower the risk of depression caused by emotional fluctuations, and is suitable for daily health care of healthy people;

1. Pain relief and physical-mental comfort: It can relieve muscle and bone pain, improve physical discomfort, achieve the overall regulatory effect of "light body and smooth mind", and indirectly assist in depression recovery;

1. Anti-carcinogenesis and anti-inflammation: By repairing abnormally proliferating cells (swollen cells), blocking carcinogenic pathways, and resisting the invasion of systemic sterile inflammation, it reduces the risk of inflammation-related diseases (e.g., arthritis, cardiovascular diseases);

1. Health enhancement: Long-term intake can improve the quality of life and extend effective lifespan, realizing the leap from disease treatment to health promotion.

4 Discussion

4.1 Scientific Explanation of Antidepressant Mechanism

The core of the antidepressant effect of T. patula extract lies in the dual mechanism of "anti-inflammation-neuroprotection": on the one hand, its total flavonoid components (e.g., patuletin, quercetagetin) can directly inhibit microglial activation, block inflammatory pathways such as TLR4/NF-κB, reduce the release of pro-inflammatory cytokines, and curb neuroinflammation at the source; on the other hand, it repairs brain synaptic damage caused by sterile inflammation, improves neurotransmitter transmission (e.g., serotonin, dopamine), and restores emotional regulatory function. This is highly consistent with the antidepressant mechanism of "natural extracts targeting ADK to inhibit neuroinflammation" discovered by the team from China Pharmaceutical University, further confirming the core position of anti-inflammatory pathways in the research of natural antidepressant drugs.

4.2 Comparative Advantages over Existing Treatment Regimens

Compared with traditional antidepressant drugs, T. patula extract has three major breakthroughs: first, "integration of prevention and treatment", which can be used both for patient treatment and as a depression preventive for healthy people; second, "pleiotropic synergy", which improves physical health and emotional state while treating depression, avoiding the limitation of "valuing spirit over body" caused by single treatment; third, "low-threshold popularization", whose low-cost and easy-to-use characteristics enable it to cover a wider population, especially suitable for depression prevention and control needs in developing countries.

4.3 Application Prospects and Precautions

The application scenarios of T. patula extract can cover three levels: 1) Clinical treatment: As a first-line treatment drug for mild to moderate depression or an adjuvant treatment for severe depression; 2) Daily health care: Added to functional foods and beverages to provide depression prevention programs for high-pressure groups (e.g., professionals, students); 3) Special population intervention: Achieving precise prevention and control for high-risk groups such as people with unstable emotions and chronic inflammation patients.

It should be noted that special populations (pregnant women, people with allergic constitutions, and those with impaired liver and kidney functions) should use it under professional guidance to avoid blind intake; at the same time, the long-term efficacy and dosage optimization of the extract still need to be further verified by large-sample clinical studies. In the future, preparation technologies (e.g., microencapsulation) can be combined to improve its stability and bioavailability.

5 Conclusion

Based on the core research results of Professor Cai Decheng's team, the total flavonoid extract from Tagetes patula L. achieves significant antidepressant effects through targeted regulation of neuroinflammatory pathways, and has the core advantages of non-toxicity, convenience, and low cost. Its pleiotropic values (emotional regulation, pain relief, anti-carcinogenesis, anti-inflammation) make it beyond the scope of single antidepressant drugs, becoming a natural solution balancing disease treatment and health promotion. With the advancement of industrial production and in-depth clinical research, T. patula extract is expected to become a new global weapon for depression prevention and control, helping humans get rid of depression and achieve dual improvement of mental health and overall health.